U.S. patent number 5,597,552 [Application Number 08/167,558] was granted by the patent office on 1997-01-28 for dentinal desensitizing compositions.
This patent grant is currently assigned to Block Drug Company Inc.. Invention is credited to James K. Herms, Kenneth J. Markowitz.
United States Patent |
5,597,552 |
Herms , et al. |
January 28, 1997 |
Dentinal desensitizing compositions
Abstract
A composition containing a water soluble or water swellable
polyelectrolyte mixed salt in a dentifrice base or other oral
compositions which can be used for relieving pain and discomfort
caused by hypersensitive teeth.
Inventors: |
Herms; James K. (Jersey City,
NJ), Markowitz; Kenneth J. (Fanwood, NJ) |
Assignee: |
Block Drug Company Inc. (Jersey
City, NJ)
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Family
ID: |
25207656 |
Appl.
No.: |
08/167,558 |
Filed: |
December 14, 1993 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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811811 |
Dec 20, 1991 |
5270031 |
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Current U.S.
Class: |
424/49; 424/641;
424/643; 424/642 |
Current CPC
Class: |
A61K
8/27 (20130101); A61Q 11/00 (20130101); A61K
8/19 (20130101); A61P 1/02 (20180101); A61P
25/02 (20180101); A61K 8/8147 (20130101) |
Current International
Class: |
A61Q
11/00 (20060101); A61K 8/72 (20060101); A61K
8/81 (20060101); A61K 8/896 (20060101); A61K
8/895 (20060101); A61K 8/19 (20060101); A61K
8/27 (20060101); A61K 007/16 (); A61K 031/315 ();
A61K 033/30 (); A61K 031/78 () |
Field of
Search: |
;424/49-58 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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200508 |
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Dec 1986 |
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EP |
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549281 |
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Jun 1993 |
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EP |
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2670383 |
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Jun 1992 |
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FR |
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2239601 |
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Jul 1991 |
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GB |
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Other References
Mason et al Clinical Prevention Denstr, vol. 12 No. 6:6-12 Jan.
1991 Evaluation of Tartar Control Dentifrices in In Vitro Models of
Dentin Sensitivity..
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Primary Examiner: Rose; Shep K.
Attorney, Agent or Firm: Ostrolenk, Faber, Gerb &
Soffen, LLP
Parent Case Text
BACKGROUND OF THE INVENTION
This is a continuation-in-part of application Ser. No. 07/811,811,
filed Dec. 20, 1991, and now U.S. Pat. No. 5,270,031.
Claims
What is claimed is:
1. In a gel or paste dentrifice containing a desensitizing amount
of a desensitizing agent, the improvement which consists
essentially of the desensitizing agent being at least one water
soluble or water swellable alkali metal or ammonium salt of an
acrylic acid polymer containing about 0,005-0.4 mole equivalent of
zinc and in which the dentrifice does not contain an additional
desensitizing agent, said desensitizing amount being sufficient to
reduce dentinal fluid flow.
2. The dentrifice of claim 1 in which the amount of the member of
the group is about 0.015 to 0.25 mole equivalent.
3. The dentrifice of claim 1 in which the alkali metal cation is
sodium.
4. The dentrifice of claim 1 in which the amount of desensitizing
agent is about 0.1 to 30% by weight of the composition.
5. The dentrifice of claim 4 in which the amount is about 1 to 15%
by weight.
6. The dentrifice of claim 5 in which the amount is about 2 to 12%
by weight.
7. In a method of desensitizing teeth by applying thereto a
desensitizing amount of a dentrifice containing a desensitizing
agent, the improvement which comprises employing the dentrifice of
claim 1 as the dentrifice.
8. In a method of desensitizing teeth by applying thereto a
desensitizing amount of a dentrifice containing a desensitizing
agent, the improvement which comprises employing the dentrifice of
claim 2 as the dentrifice.
9. In a method of desensitizing teeth by applying thereto a
desensitizing amount of a dentrifice containing a desensitizing
agent, the improvement which comprises employing the dentrifice of
claim 3 as the dentrifice.
10. In a method of desensitizing teeth by applying thereto a
desensitizing amount of a dentrifice containing a desensitizing
agent, the improvement which comprises employing the dentrifice of
claim 4 as the dentrifice.
11. In a method of desensitizing teeth by applying thereto a
desensitizing amount of a dentrifice containing a desensitizing
agent, the improvement which comprises employing the dentrifice of
claim 5 as the dentrifice.
12. In a method of desensitizing teeth by applying thereto a
desensitizing amount of a dentrifice containing a desensitizing
agent, the improvement which comprises employing the dentrifice of
claim 6 as the dentrifice.
13. The dentrifice of claim 2 in which the polymer is a
cross-linked homopolymer having a molecular weight of 450,000 to
4,000,000 which is about 40-90% mole equivalently neutralized.
14. In a method of desensitizing teeth by applying thereto a
desensitizing amount of a dentrifice containing a desensitizing
agent, the improvement which comprises employing the dentrifice of
claim 13 as the dentrifice.
Description
Hypersensitive teeth can cause pain and discomfort when subjected
to changes in temperature, pressure, or chemical action. Exposure
of the dentin frequently leads to hypersensitivity. Dentin exposure
may occur due to recession of the gums, periodontal disease and
improper dental care. The usual method of treating hypersensitive
teeth employs a desensitizing dentifrice or solution. Some of the
active ingredients used in desensitizing dentifrices include
strontium chloride, strontium acetate, potassium nitrate, and
potassium chloride. Other treatments are applied professionally as
a solution. These include solutions of ferric oxalate or potassium
oxalate.
One approach to desensitization is to occlude exposed dentinal
tubules. Dentinal tubules lead from the pulp to the surface of the
dentin. When the surface of the tooth is eroded, the dentinal
tubules become exposed to the external environment. The exposed
dentinal tubules provide a pathway for transmission of fluid flow
to the pulpal nerves and this is induced by changes in temperature,
pressure and ionic gradients. By blocking the tubules, the external
stimuli have a diminished effect, and less pain will be felt.
Some active ingredients, such as ferric oxalate, are known to form
mineral deposits on the surfaces of exposed dentinal tubules,
effectively blocking the openings. In some cases, the abrasive
action from brushing may cause a smear layer to form over the
surface of the tooth and thus plug up the open tubules. The
accumulation of particulate matter from the interstitial fluid
passing through the dentinal tubules or remineralization within the
tubules can cause a natural occlusion of the tubules.
Nerve inactivation is another mechanism whereby desensitization can
occur. This relies on the action of an active ingredient such as
potassium nitrate on the nerves. By altering the ionic balance in
the nerve, the threshold of nerve stimulation is increased. Thus a
higher level of stimulation is needed to evoke a painful
response.
The materials which have been used as active ingredients in the
treatment of hypersensitive teeth are generally inorganic salts or
hydrophobic compounds. Although hydrophilic polymers have been used
in oral compositions as excipients or the like, they have not been
suggested as being useful active ingredients for desensitization
purposes. Most of the hydrophilic polymers have been used to
control the viscosity of the oral formulation or to give it
thixotropic properties.
An example of such a polymer is polyacrylic acid which is used as a
thickener in dentifrice formulations. It has also been used in
gels, mouthwashes and buccal adhesive patches. However, polyacrylic
acid has also been used for other purposes. For example, Leonard et
al. (U.S. Pat. No. 5,011,830) state an oral composition containing
an alkali pyrophosphate salt, a fluoride salt and a polyacrylic
acid or a copolymer of acrylic acid and another monomer can provide
enhanced anti-calculus benefits. Gaffar (U.S. Pat. No. 3,956,480)
uses an anionic polymer such as polyacrylic acid with chlorhexidine
as an anti-calculus agent. Benedict and Sunberg (U.S. Pat. No.
4,661,341) describe the use of polyacrylic acid or copolymers of
polyacrylic acid as anti-calculus agents. In none of the examples
above or elsewhere, as far as we are aware, are these polymers
claimed to provide a desensitizing effect.
It has now been determined that certain water soluble or water
swellable polyelectrolytes, i.e. polymers with functional groups
that are capable of bearing one or more charged groups in an
aqueous solution have desensitizing properties.
It is accordingly the object of this invention to provide new
dentinal desensitizing agents. This and other objects of the
invention will become apparent to those skilled in this art from
the following detailed description.
SUMMARY OF THE INVENTION
This invention relates to an oral composition and method which is
useful for relieving pain and discomfort caused by hypersensitive
teeth. More particularly, the invention relates to the use of
certain water soluble or water swellable polyelectrolyte partial
salts as a dental desensitization agent. The cations used to make
the salt can include ammonium, alkylammonium, calcium, sodium,
potassium, strontium, magnesium, zinc, aluminum, tin, iron, barium,
lanthanum, titanium, bismuth and copper. The salts may contain
single cations or mixed cations.
The polymer and its salts may be formulated into a dentifrice, gel,
buccal adhesive patch, mouthwash, lozenge, or gum. Use of these
oral compositions on a regular basis can provide relief from the
pain and discomfort of hypersensitive teeth. The oral composition
described above may also provide for a sustained release mode of
action for the delivery of strontium or potassium ions from the
water soluble or water swellable polyelectrolytes. The
polyelectrolytes may also be used in conjunction with additional
desensitizing agents such as strontium chloride or potassium
nitrate in an oral composition. In addition a source of fluoride
ion can be incorporated into the composition.
DESCRIPTION OF THE INVENTION
In accordance with the present invention, a water soluble or water
swellable polyelectrolyte partial salt is used as a dentinal
desensitizing agent. The agent can be incorporated into a
dentrifice, gel, mouthwash, lozenge, buccal adhesive patch, gum or
the like. The water soluble or swellable polymer is an acrylic acid
polymer (which term includes acrylic acid copolymers). Polyacrylic
acid can be obtained, for instance, from B. F. Goodrich under the
tradename Carbopol.RTM. or Noveon.RTM. as a cross-linked
polyacrylic acid generically catagorized as carbomer or
polycarbophil. Polyacrylic acid can also be obtained from Rohm and
Haas under the tradename Acusol.TM..
The commercially available polymers are produced over a range of
molecular weights. Thus, for instance, Carbopol.RTM. and
Noveon.RTM. are available in different grades with different
rheological properties. The different grades range in molecular
weight from 450,000 (907 type) to 4,000,000 (980 type). It is
preferable to employ the highest molecular weight grade consistent
with the viscosity of the formulation being prepared and
concentration of the agent. The formulations will contain a
desensitizing amount which is generally from about 0.1% to 30% by
weight of the polymer partial salt, with about 1-15% being
preferred and about 2-12% most preferred. For any given
concentration, viscosity generally increases with molecular weight
and for any given molecular weight, viscosity generally increases
with concentration.
The properties of the polyacrylic acid are modified to obtain the
most advantageous properties by partial neutralization. The cations
may be present in the salts at about 20% to 100% equivalent mole
ratio of the polymer. The preferred range is from about 40% to 90%
equivalent of the polymer. The cations that can be used include
ammonium, alkylammonium, calcium, sodium, potassium, strontium,
zinc, aluminum, magnesium, tin, iron, barium, lanthanum, titanium,
bismuth and copper. The cations can be used singly or as a mixture
of different cations. These salts as such are well known in the
art.
The salts of the polymer can be made by making a solution of the
polymer in water and then adding ammonia or a metal salt such as
the hydroxide, carbonate, bicarbonate, oxide, acetate, citrate,
lactate, formate or phosphate. The metal salt is preferably
alkaline. The solution is stirred, with heating if necessary, until
the polymer has dissolved. It will usually have a pH between about
3.5 and 9, depending on the amount of metal salt used. The salt
solution can be directly incorporated into an aqueous oral
composition. Alternatively, the solution can be evaporated to
dryness to give a solid salt which can be milled to a fine powder,
if desired, and incorporated into an oral composition.
In order to modify the physical properties of the oral composition,
it is preferred to utilize an alkali metal or ammonium salt of the
polyelectrolyte partially substituted with 0,005 to 0.4, preferably
0,015 to 0.25, mole equivalent of calcium, zinc or other
multivalent (divalent or polyvalent) cation. These cations may
include but are not limited to zinc, tin, magnesium, strontium,
copper, iron, bismuth, aluminum and bis(biguanidinium). Adding the
cation in such a way as to favor intramolecular crosslinking can
have the advantage of reducing the viscosity and hence improving
the organoleptic characteristics of the oral composition without
hindering the ability of the composition to reduce dentin fluid
flow.
Oral compositions describing polyacrylate polymers partially
substituted with multivalent metal salts have been described.
Gaffar in U.S. Pat. No. 4,138,477 discloses the use of zinc polymer
combinations formed by the reaction or interaction of zinc compound
with an anionic polymer as oral compositions to control mouth odor.
The purpose of that invention is to have the complex adhere to the
tissues of the oral cavity where slow release of zinc occurs.
U.S. Pat. No. 4,296,096 to Pierce describes the preparation of a
high viscosity dentifrice containing a polyelectrolyte polymer
ionically crosslinked with aluminum or other polyvalent cation to
form particles less than 74 microns in size. These particles act as
a water absorbing insoluble gel and serve as a dentifrice
humectant. Zinc is mentioned as one of the ionic crosslinking
agents. The methods of ion-polymer mixing described would result in
extensive intermolecular crosslinking of the polymer. In the
present invention, zinc is added under conditions which would favor
intramolecular crosslinking for the purpose of deswelling of the
polyacrylic acid gel.
In order to obtain the desired physical properties the following
general procedure has to be used to fabricate the partially
substituted polyacrylic acid salt.
First a resin power is dispersed into an acidified aqueous solution
containing the desired quantities of the divalent or polyvalent
metal salt. Other desensitizing salts such as KNO.sub.3 can be
present in the acidified solution as well. After hydration of the
resin is complete, a slurry of an abrasive may be added under high
shear. The pH of the dispersion may be adjusted to the desired
value by the rapid addition of an alkaline neutralizing agent under
high shear. In order to obtain the desired physical properties it
is important to raise the pH of the dispersion rapidly, e.g., at
least four pH units per minute. Finally the foaming agent,
fluoride, flavors and other desired ingredients are blended in.
The polymer salt can be formulated into a dentifrice, mouthwash,
lozenge, buccal adhesive patch or gum using ingredients and
procedures which are well known and commonly used in preparing
these oral compositions. By way of example, without limitation, it
is possible to incorporate a fluoride source into the oral
composition. Of course, the ingredients used to make the above oral
compositions should be compatible with the polymer and its salts.
It is also possible to formulate the oral compositions in
conjunction with additional desensitizing agents. Additional
desensitizing agents include, without limitation, sodium fluoride,
sodium silicofluoride, zinc chloride, formaldehyde, glycerin and
silver nitrate. Additional desensitizing agents may also include
potassium-containing compounds, such as potassium nitrate, as
described in U.S. Pat. No. 3,863,006 and strontium-containing
compounds, such as strontium chloride, as described in U.S. Pat.
No. 3,122,483.
The polyacrylic acid partial salts have an affinity for the tooth
surface and can maintain their presence over a period of time. This
allows for a longer term availability of the actives for
desensitization.
In order to further illustrate the present invention, various
non-limiting examples are set forth below. In these examples, as
throughout this specification and claims, all temperatures are in
degrees centigrade and all parts and percentages are by weight
unless otherwise indicated.
EXAMPLE 1
A gel containing a sodium (80% equivalent) salt of polyacrylic acid
was prepared from the following ingredients:
______________________________________ INGREDIENT % WEIGHT
______________________________________ Polyacrylic Acid 2.9% Sodium
hydroxide 1.3% Glycerin 21.0% Potassium Nitrate 5.0% Water 69.6%
Sodium Fluoride 0.2% ______________________________________
EXAMPLE 2
A dentrifice containing 5% polyacrylic acid (85% equivalent sodium
salt) was prepared from the following ingredients:
______________________________________ INGREDIENT % WEIGHT
______________________________________ Carbomer 4.0% Sodium
hydroxide 1.8% Glycerin 20.0% Potassium Nitrate 5.0% Silica 3.9%
Poloxamer 237 2.5% Flavors & Preservatives 0.7% Water 61.9%
Sodium Fluoride 0.2% ______________________________________
EXAMPLE 3
A mouthwash was made by mixing the following ingredients:
______________________________________ INGREDIENT % WEIGHT
______________________________________ Polyacrylic acid (Na/Zn
salt) 2.0% Alcohol 190 Proof 4.0% (Grain Alcohol) Sorbitol 10.0%
Poloxamer 407 2.0% Flavor 0.3% Water 81.7%
______________________________________
EXAMPLE 4
A desensitizing gel dentifrice with fluoride was prepared from the
following ingredients:
______________________________________ Carbomer 4.2% Zinc sulfate
0.7% Hydrochloric acid, 37% 0.2% Potassium nitrate 5.0% Sodium
hydroxide 2.2% Sodium fluoride 0.2% Glycerin 20.0% Hydrated silica
5.0% Poloxamer 237 2.5% Flavors & preservatives 1.5% Water
58.5% ______________________________________
EXAMPLE 5
A desensitizing gel dentifrice with fluoride was prepared from the
following ingredients:
______________________________________ Polyacrylic acid 4.0% Zinc
sulfate 0.5% Hydrochloric acid, 37% 0.1% Sodium hydroxide 2.0%
Sodium fluoride 0.2% Glycerin 20.0% Hydrated silica 4.0%
Cocamidopropyl betaine, 30% 6.0% Flavors & preservatives 1.5%
Water 61.7% ______________________________________
EXAMPLE 6
A desensitizing paste dentrifrice was prepared from the following
ingredients:
______________________________________ Polyacrylic acid 4.2% Zinc
sulfate 0.7% Hydrochloric acid, 37% 0.2% Potassium nitrate 5.0%
Sodium hydroxide 2.2% Sodium fluoride 0.2% Glycerin 16.5% Calcium
pyrophosphate 10.0% Cocamidopropyl betaine, 30% 7.0% Flavors &
preservatives 1.5% Water 52.5%
______________________________________
EXAMPLE 7
A desensitizing paste dentifrice was prepared from the following
ingredients:
______________________________________ Polycarbophil 4.2% Calcium
chloride 0.5% Hydrochloric acid, 37% 0.2% Potassium chloride 3.7%
Sodium hydroxide 2.2% Glycerin 17.0% Calcium pyrophosphate 10.0%
Cocamidopropyl betaine, 30% 7.0% Flavors & preservatives 1.5%
Water 53.7% ______________________________________
EXAMPLE 8
A desensitizing chewing gum was prepared from the following
ingredients:
______________________________________ Polyacrylic acid 1.5%
(sodium, zinc) salt Potassium chloride 1.6% Sodium fluoride 0.01%
Gum base 40.0% Lecithin 0.5% Flavor 1.0% Mannitol 3.0% Sorbitol
52.39% ______________________________________
EXAMPLE 9
A desensitizing oral lozenge was prepared from the following
ingredients:
______________________________________ Polyacrylic acid sodium salt
1.5% Zinc chloride 0.1% Sodium fluoride 0.01% Flavor 0.5% Sorbitol
97.89% ______________________________________
Tests Of Oral Compositions Of Examples
The prepared solutions and oral compositions were tested using the
method described by Pashley (J. Periodontology, Vol. 55, No. 9, p.
522, September 1984). This test measures the flow of fluid through
a sliced dentin disc. A treatment that will reduce the flow through
the discs can also result in reduced dentinal hypersensitivity for
people using the treatment.
A caries free tooth is sliced to obtain a 0.4 to 0.6 mm thick
dentin disc. The disc is mounted in a split chamber device (J.
Dent. Research 57:187, 1978). The initial flow of fluid through the
disc is measured, and then the disc is treated by brushing with one
of the desensitizing treatments. After brushing, the flow rate is
again measured and the reduction in flow is calculated from these
measurements. The following compositions were used and the
reduction in flow is reported. The results for the dentifrices are
based on 1 to 1 dilution with artificial or human saliva.
______________________________________ Treatment % Change in Flow
______________________________________ Example 1 -48% Example 2
-63% Example 4 -97% Example 7 -80%
______________________________________
Various changes and modifications can be made in the process and
products of this invention without departing from the scope
thereof. The various embodiments described herein were for the
purpose of further illustrating the invention but were not intended
to limit it.
* * * * *